Genetic Parameter Estimates for Metabolizing Two Common Pharmaceuticals in Swine.

Area of Science:

• Animal Genetics
• Pharmacokinetics
• Livestock Science

Background:

• Drug regulation in livestock is increasingly scrutinized.
• The genetic contribution to drug metabolism variation in animals remains largely unquantified.
• Understanding genetic influences is crucial for optimizing drug efficacy and safety in livestock.

Purpose of the Study:

• To determine the proportion of phenotypic variation in fenbendazole and flunixin meglumine metabolism attributable to genetics in pigs.
• To estimate heritability for drug and metabolite concentrations over time and via pharmacokinetic parameters.

Main Methods:

• A population of 198 crossbred pigs was used.
• Drugs were administered intravenously, with blood samples collected over 48 hours.
• Pharmacokinetic (PK) parameters and drug concentrations over time were analyzed using a random regression model incorporating sire and batch effects.

Main Results:

• Mean heritability estimates for fenbendazole and flunixin meglumine parent drugs (metabolites) were 0.15 (0.18) and 0.31 (0.40) across PK parameters, respectively.
• Mean heritability estimates across time were 0.27 (0.60) for fenbendazole and 0.14 (0.44) for flunixin meglumine, respectively.
• Random regression models using plasma drug concentrations over time yielded smaller standard errors compared to PK-parameter-based models.

Conclusions:

• Genetics explain a low to moderate proportion of phenotypic variation in fenbendazole and flunixin meglumine metabolism in pigs.
• Random regression models utilizing plasma drug concentrations over time provided more precise heritability estimates.
• Findings highlight the genetic component influencing drug metabolism in livestock, informing future breeding and drug use strategies.